A new study provides real-world evidence supporting potential repurposing of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used to treat type 2 diabetes and obesity to prevent Alzheimer's disease (AD ) can be used.

Adults with type 2 diabetes who were prescribed the GLP-1 RA semaglutide had a significantly lower risk of AD compared to their peers who were prescribed one of seven other antidiabetic medications, including other types of medications targeting the GLP-1 receptor.

“These results support further clinical trials to evaluate the potential of semaglutide in delaying or preventing AD,” write the researchers, led by Rong Xu, PhD, of Case Western Reserve School of Medicine, Cleveland, Ohio.

The study was published online on October 24th Alzheimer's and dementia.

Real world data

Semaglutide has demonstrated neuroprotective effects in animal models of neurodegenerative diseases, including AD and Parkinson's disease. In animal models of AD, the drug reduced beta-amyloid deposition and improved spatial learning and memory, as well as glucose metabolism in the brain.

In a real-world analysis, Xu and colleagues used electronic health records to identify 17,104 new users of semaglutide and 1,077,657 new users of seven other antidiabetic drugs, including other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporters -2 inhibitors, sulfonylurea and thiazolidinedione.

Over three years, treatment with semaglutide was associated with a significantly reduced risk of developing AD, most strongly compared to insulin (hazard ratio (HR) 0.33) and weakest compared to other GLP-1 agents. RAs (HR 0.59).

Compared to the other medications, semaglutide was associated with a 40% to 70% reduced risk of a first diagnosis of AD in patients with type 2 diabetes, with similar reductions observed across obesity statuses as well as gender and age groups, the authors reported.

The results are consistent with current evidence suggesting that GLP-1 RAs may protect cognitive function.

For example, as previously reported by Medscape Medical NewsIn the Phase 2b ELAD clinical trial, adults with early-stage AD who took the GLP-1 RA liraglutide showed slower decline in memory and thinking and experienced less brain atrophy compared to placebo over 12 months.

Promising, but preliminary

Reached for comment, Courtney Kloske, PhD, director of scientific engagement for the Alzheimer's Association, noted that diabetes is a known risk factor for AD and that treating diabetes with drugs such as semaglutide “by treating diabetes alone can impair the health of the patient.” “could improve the brain”.

“However, we still need large clinical trials in representative populations to determine whether semaglutide specifically reduces the risk of Alzheimer's disease. Therefore, it is still too early to recommend it for prevention,” said Kloske Medscape Medical News.

She noted that some research suggests that GLP-1 RAs “may help reduce inflammation and positively influence brain energy consumption.” However, more research is needed to fully understand how these processes do this “could help prevent cognitive decline or Alzheimer’s,” warned Kloske.

The Alzheimer's Association's Part the Cloud initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that address known and potentially new aspects of the disease could, said Kloske.

The study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. Xu and Kloske have no relevant conflicts.